tbuckley/cabot-search huggingface dataset:
Oral Presentation No. 083 Coronary Aspiration Thrombectomy: bringing back the old kid on the block
Authors: António Rocha de Almeida, David Neves, Marta Figueiredo, Miguel Carias Sousa, Francisco Cláudio, Rita Rocha, Manuel Trinca
Journal: Cardiovascular Research (2022)

Abstract Background Traditionally, routine thrombus aspiration during primary percutaneous coronary intervention (PCI) was performed to prevent distal embolization and protect microvascular perfusion. However, recent trials showed no clinical benefits (except if high thrombotic burden). Despite not being routinely recommended, thrombus aspiration should still be considered in highly thrombotic circumstances. Material and methods Prospective cohort of 50 patients admitted to primary PCI, with aspiration thrombectomy (AT), between 2019–2022, was analyzed. In evidence of high thrombotic burden, AT was performed, if technically possible. Success was evaluated angiographically and by TIMI flow improvement. Safety was assessed by neurologic evaluation, verified CT-scan, in 30 days follow-up. Results and conclusions 50 patients were analyzed, with mean age of 59,6 ± 1,8 years, being 22% women (n = 11). 88% (n = 44) presented ST-segment elevation myocardial infarction Killip 1, 2% (n = 1) Killip 3 and 10% (n = 5) Killip 4. There was thrombus aspiration angiographic evidence in 76% (n = 38) and TIMI flow increase in 82% (n = 41) cases with median improvement of 2 [IR 1,3]. In 20% (n = 10) cases, stent wasn't implanted. There was significant statistical association between no stent PCI and angiographical thrombus reduction (P &amp;lt; 0,05, OR 3,86). There were no deaths, major adverse cardiovascular events (MACE), or neurologic complications in any patient (n = 0) within 30 days. Routine coronary AT shouldn't be performed. It is useful, however, in selected cases with evidence of angiographic thrombus aspiration and TIMI flow improvement. Successful AT was associated with no stent PCI. Regarding safety, there was no statistically significant increase of death of any cause, MACE, or stroke.
Poster No. 045 The role of 24-h Holter monitoring in thrombosis – a single-centre subanalysis in the young
Authors: Carolina Miguel Gonçalves, Adriana Vazão, Mariana Carvalho, Sara Fernandes, Margarida Cabral, Rita Carvalho, Hélia Martins, Fátima Saraiva, João Morais
Journal: Cardiovascular Research (2022)

Abstract Background Undercovering the etiology responsible for pathologic states is of the uttermost importance, especially regarding young people. Arterial and venous thromboembolism may have an impact on morbidity and mortality, enhancing the need to prevent recurrences. Material and methods Retrospective, single-centre analysis of 24-h Holter monitoring in patients with thrombotic events and less than 40 years during a 5-year period, using IBM® SPSS® software to perform descriptive analysis. Results and conclusions Thrombosis was the reason for requesting 24-h Holter monitoring in 7% (n = 41) from a total of 581 exams screened – 68.3% had a stroke, 6% a transient ischemic stroke, 4.9% a pulmonary embolism, 4.9% an intestinal ischemia and 2.4% had both pulmonary embolism and deep vein thrombosis. Patients had a median age of 35 ± 6 years, 63.7% were male and past medical history consisted of cardiovascular risk factors, particularly smoking (36.6%), high blood pressure (19.5%) and dyslipidemia (12.2%). Merely 4.9% had a diagnostic finding – atrial flutter and second-degree atrioventricular block Mobitz II. On the other hand, autoimmune tests were altered in 12.2% and echocardiogram revealed patent foramen ovale, atrial septum aneurysm and interatrial septum bulging with shunt in 9.8%, 2.4% and 2.4%, respectively. Regarding management, 78% were medicated with aspirin or anticoagulant and 4.9% were submitted to percutaneous closure of patent foramen ovale. Despite low prevalence of diagnostic findings, Holter monitoring is an important complementary exam that can have therapeutic implications in these cases and, consequently, in preventing new events.
Poster No. 113 Case report: the challenges in diagnosing congenital double-chambered left ventricle in adults
Authors: Mengfei Lu, Joseph Appiah, Mae-Sing Lim-Cooke
Journal: Cardiovascular Research (2022)

Abstract Background Double-chambered left ventricle is a congenital condition that rarely presents in adulthood. This case report illustrates the common cardiac imaging modalities and presents the diagnostic challenges. Material and method Clinical history and cardiac imaging was obtained using electronic systems and E-letters. Literature search was performed using PubMed with keywords including double-chambered ventricle and congenital heart disease. Discussion A 76-year-old female presented with breathlessness, her transthoracic echocardiogram (TTE) showed severely impaired bi-ventricular function. An incidental echogenic structure was identified and treated initially as a left ventricular (LV) thrombus. Follow-up cardiac magnetic resonance (CMR) with perfusion confirmed the LV apical mass, but thought was more in keeping with a tumour. Further investigations with a gated cardiac Computerised Tomography (CT) and a review of the original CMR demonstrated appearances that were consistent with a developmental congenital double-chambered left ventricle rather than a false aneurysm or thrombus. This was confirmed on repeat CMR and with enhancement and transoesophageal echocardiogram (TOE) on 3D reconstruction. A discussion between Cardiologist and Cardiac Surgeons concluded that she is unlikely to benefit from any surgical intervention. The patient has since had significant improvement in LV function with medical therapy. Conclusions This report highlights an interesting case where congenital double-chambered left ventricle can act as a mimic for left ventricular thrombus or tumour. Current cardiac imaging modalities can be used in combination to achieve the diagnosis. It also demonstrates that pharmacological therapy alone is an adequate treatment to manage the symptoms of severely impaired bi-ventricular function in these patients.
Poster No. 137 A very evident pulmonary thrombus
Authors: Catarina Gonçalves Coelho, Mariana Saraiva, Joana Luís, Sofia Lázaro Mendes, Maria Luz Pitta, Vítor Paulo Martins
Journal: Cardiovascular Research (2022)

Abstract Clinical case Female patient, 78 years-old, that complained of epigastric pain and intense fatigue for a week. While waiting in the urgency department, she became hypotensive, with refractory shock. Electrocardiogram showed sinus rhythm, 90 bpm, de novo right bundle block and infraST in the right precordial leads. The echocardiogram showed a dilated right ventricle (ratio RV/LV &amp;gt; 1), with depressed function and major tricuspid regurgitation, RV/RA gradient of at least 55 mmHg. Left ventricle presented “D-shape”, preserved function and no segmental kinetic changes. The pulmonary artery was dilated and a serpentiform mass was visible, protruding through the pulmonary valve; similar masses were also visible in its branches. The diagnosis of pulmonary embolism (PE) was assumed and fibrinolysis was started, given there were no contra-indications. One year before, she had an intermediate-risk PE in the context of COVID-19, with a similar echocardiographic presentation. She recovered RV function in the following months and stopped anticoagulation 3 months after that episode. Discussion PE can present with varying degrees of severity. Bedside echocardiography can be of major help in its diagnosis, especially in critical patients. The visualization of a thrombus in the pulmonary artery is rare, particularly in transthoracic echocardiogram. Echocardiogram is also useful for risk stratification and prognostic evaluation. This patient developed obstructive shock due to massive PE and the fibrinolytic treatment was paramount for her survival. A good echocardiogram helped in the differential diagnosis and enabled the Cardiologist to assist the patient in the best way.
Combining precision oncology and immunotherapy by targeting the MALT1 protease
Authors: Thorsten R Mempel, Daniel Krappmann
Journal: Journal for ImmunoTherapy of Cancer (2022)

An innovative strategy for cancer therapy is to combine the inhibition of cancer cell-intrinsic oncogenic signaling with cancer cell-extrinsic immunological activation of the tumor microenvironment (TME). In general, such approaches will focus on two or more distinct molecular targets in the malignant cells and in cells of the surrounding TME. In contrast, the protease Mucosa-associated lymphoid tissue protein 1 (MALT1) represents a candidate to enable such a dual approach by engaging only a single target. Originally identified and now in clinical trials as a lymphoma drug target based on its role in the survival and proliferation of malignant lymphomas addicted to chronic B cell receptor signaling, MALT1 proteolytic activity has recently gained additional attention through reports describing its tumor-promoting roles in several types of non-hematological solid cancer, such as breast cancer and glioblastoma. Besides cancer cells, regulatory T (Treg) cells in the TME are particularly dependent on MALT1 to sustain their immune-suppressive functions, and MALT1 inhibition can selectively reprogram tumor-infiltrating Treg cells into Foxp3-expressing proinflammatory antitumor effector cells. Thereby, MALT1 inhibition induces local inflammation in the TME and synergizes with anti-PD-1 checkpoint blockade to induce antitumor immunity and facilitate tumor control or rejection. This new concept of boosting tumor immunotherapy in solid cancer by MALT1 precision targeting in the TME has now entered clinical evaluation. The dual effects of MALT1 inhibitors on cancer cells and immune cells therefore offer a unique opportunity for combining precision oncology and immunotherapy to simultaneously impair cancer cell growth and neutralize immunosuppression in the TME. Further, MALT1 targeting may provide a proof of concept that modulation of Treg cell function in the TME represents a feasible strategy to augment the efficacy of cancer immunotherapy. Here, we review the role of MALT1 protease in physiological and oncogenic signaling, summarize the landscape of tumor indications for which MALT1 is emerging as a therapeutic target, and consider strategies to increase the chances for safe and successful use of MALT1 inhibitors in cancer therapy.
Antitumor strategies targeting macrophages: the importance of considering the differences in differentiation/polarization processes between human and mouse macrophages
Authors: Marine Monnier, Léa Paolini, Emeline Vinatier, Alberto Mantovani, Yves Delneste, Pascale Jeannin
Journal: Journal for ImmunoTherapy of Cancer (2022)

Macrophages are the immune cells that accumulate the most in the majority of established tumors and this accumulation is associated with a poor prognosis. Tumor-associated macrophages (TAMs) produce inflammatory cytokines and growth factors that promote tumor expansion and metastasis. TAMs have recently emerged as targets of choice to restore an efficient antitumor response and to limit tumor growth. Many molecules targeting TAMs are actually evaluated in clinical trials, alone or in combination. While these molecules induce tumor regression and stimulate cytotoxic responses in mouse models of tumor development, results from early clinical trials are less impressive. In this review, we list the biological differences between human and mouse macrophages that help explain the different efficacy of antitumor strategies targeting TAMs between human and animal studies. Differences in the impact of survival and polarization factors and in the cytokines produced and markers expressed as well as the limitations of extrapolations based on in vitro models of TAM-like generation should be considered in order to improve the design and efficacy of antitumor drugs targeting TAMs.
Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history
Authors: Wei Wang, Sabrina Lusvarghi, Rahul Subramanian, Nusrat J. Epsi, Richard Wang, Emilie Goguet, Anthony C. Fries, Fernando Echegaray, Russell Vassell, Si’Ana A. Coggins, Stephanie A. Richard, David A. Lindholm, Katrin Mende, Evan C. Ewers, Derek T. Larson, Rhonda E. Colombo, Christopher J. Colombo, Janet O. Joseph, Julia S. Rozman, Alfred Smith, Tahaniyat Lalani, Catherine M. Berjohn, Ryan C. Maves, Milissa U. Jones, Rupal Mody, Nikhil Huprikar, Jeffrey Livezey, David Saunders, Monique Hollis-Perry, Gregory Wang, Anuradha Ganesan, Mark P. Simons, Christopher C. Broder, David R. Tribble, Eric D. Laing, Brian K. Agan, Timothy H. Burgess, Edward Mitre, Simon D. Pollett, Leah C. Katzelnick, Carol D. Weiss
Journal: Cell Host & Microbe (2022)

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.
Effectiveness and tolerance of Janus kinase inhibitors for the treatment of recalcitrant atopic dermatitis in a real-life French multicenter adult cohort
Authors: Julia Vanlerberghe, Frédéric Dezoteux, Claire Martin, Marie Jachiet, Angèle Soria, Florence Tétart, Anne-Bénédicte Modeste-Duval, Anne-Claire Bursztejn, Laurent Misery, François Aubin, Audrey Lasek, Camille Leleu, Aurélie Du-Thanh, Justine Pasteur, Pauline Pralong, Audrey Nosbaum, Catherine Droitcourt, Manuelle Viguier, Marie Tauber, Julien Seneschal, Sébastien Barbarot, Delphine Staumont-Sallé
Journal: Journal of the American Academy of Dermatology (2022)
Convergent actions of stress and stimulants via epigenetic regulation of neural circuitry
Authors: Michael D. Murphy, Elizabeth A. Heller
Journal: Trends in Neurosciences (2022)

The dorsal striatum integrates prior and current information to guide appropriate decision-making. Chronic stress and stimulant exposure interferes with decision-making, and can confer similar cognitive and behavioral inflexibilities. This review examines the literature on acute and chronic regulation of the epigenome by stress and stimulants. Recent evidence suggests that exposures to stress and stimulants share similarities in the manners in which they regulate the dorsal striatum epigenome through DNA methylation, transposable element activity, and histone post-translational modifications. These findings suggest that chronic stress and stimulant exposure leads to the accumulation of epigenetic modifications that impair immediate and future neuron function and activity. Such epigenetic mechanisms represent potential therapeutic targets for ameliorating convergent symptoms of stress and addiction.
Molecular disease mechanisms of human antineuronal monoclonal autoantibodies
Authors: Sophie L. Duong, Harald Prüss
Journal: Trends in Molecular Medicine (2022)

Autoantibodies targeting brain antigens can mediate a wide range of neurological symptoms ranging from epileptic seizures to psychosis to dementia. Although earlier experimental work indicated that autoantibodies can be directly pathogenic, detailed studies on disease mechanisms, biophysical autoantibody properties, and target interactions were hampered by the availability of human material and the paucity of monospecific disease-related autoantibodies. The emerging generation of patient-derived monoclonal autoantibodies (mAbs) provides a novel platform for the detailed characterization of immunobiology and autoantibody pathogenicity in vitro and in animal models. This Feature Review focuses on recent advances in mAb generation and discusses their potential as powerful scientific tools for high-resolution imaging, antigenic target identification, atomic-level structural analyses, and the development of antibody-selective immunotherapies.
Frequency of food allergy in Europe: An updated systematic review and meta‐analysis
Authors: Giulia C. I. Spolidoro, Yohannes Tesfaye Amera, Mohamed Mustafa Ali, Sungkutu Nyassi, Daniil Lisik, Athina Ioannidou, Graciela Rovner, Ekaterina Khaleva, Carina Venter, Ronald van Ree, Margitta Worm, Berber Vlieg‐Boerstra, Aziz Sheikh, Antonella Muraro, Graham Roberts, Bright I. Nwaru
Journal: Allergy (2022)

Food allergy (FA) is increasingly reported in Europe, however, the latest prevalence estimates were based on studies published a decade ago. The present work provides the most updated estimates of the prevalence and trends of FA in Europe. Databases were searched for studies published between 2012 and 2021, added to studies published up to 2012. In total, 110 studies were included in this update. Most studies were graded as moderate risk of bias. Pooled lifetime and point prevalence of self-reported FA were 19.9% (95% CI 16.6-23.3) and 13.1% (95% CI 11.3-14.8), respectively. The point prevalence of sensitization based on specific IgE (slgE) was 16.6% (95% CI 12.3-20.8), skin prick test (SPT) 5.7% (95% CI 3.9-7.4), and positive food challenge 0.8% (95% CI 0.5-0.9). While lifetime prevalence of self-reported FA and food challenge positivity only slightly changed, the point prevalence of self-reported FA, sIgE and SPT positivity increased from previous estimates. This may reflect a real increase, increased awareness, increased number of foods assessed, or increased number of studies from countries with less data in the first review. Future studies require rigorous designs and implementation of standardized methodology in diagnosing FA, including use of double-blinded placebo-controlled food challenge to minimize potential biases.
Highly Efficient Photodynamic Therapy with Mitochondria‐Targeting Aggregation‐Induced Emission Photosensitizer for Retinoblastoma
Authors: Lingbo Zhou, Luojia Chen, Sijie Chen, Zeyuan Pu, Meijia Gu, Yin Shen
Journal: Advanced Healthcare Materials (2022)

Retinoblastoma (RB) is an aggressive eye cancer in infancy and childhood, lethal by metastasis if left untreated. Currently, the survival rate and the chance of saving vision depend on the severity of the disease. In this work, a highly efficient photodynamic ophthalmic therapy for RB is reported by employing an isoquinolinium-based aggregation-induced-emission (AIE) photosensitizer (PS) TPE-IQ-2O for photodynamic inactivation (PDI). TPE-IQ-2O is an efficient mitochondria-targeting photosensitizer as an efficient guided photodynamic therapy (PDT) agent against cancer cells. Maximizing cancer-selectively damage to tumors with minimized side effects on normal tissue is essential for effective anticancer PDT and provides long-lasting protection against metastasis. In addition, TPE-IQ-2O can effectively reduce the degree of tissue inflammation by inhibiting the expression of related inflammatory factors. TPE-IQ-2O also exhibits excellent biocompatibility with a neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications in the treatment of RB.
Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice
Authors: Xiaoqing Fan, Chutian Mai, Ling Zuo, Jumin Huang, Chun Xie, Zebo Jiang, Runze Li, Xiaojun Yao, Xingxing Fan, Qibiao Wu, Peiyu Yan, Liang Liu, Jianxin Chen, Ying Xie, Elaine Lai-Han Leung
Journal: Acta Pharmaceutica Sinica B (2022)

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.
Palliative care and end-of-life care in adults with malignant brain tumors
Authors: Johan A F Koekkoek, Pim B van der Meer, Andrea Pace, Caroline Hertler, Rebecca Harrison, Heather E Leeper, Deborah A Forst, Rakesh Jalali, Kathy Oliver, Jennifer Philip, Martin J B Taphoorn, Linda Dirven, Tobias Walbert
Journal: Neuro-Oncology (2022)

Abstract Background This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO) guidelines for palliative care in adults with malignant brain tumors. It provides an overview of palliative care options, including during the end-of-life phase for patients with malignant brain tumors. Methods A systematic literature search was conducted from 2016 to 2021 focusing on four main topics: (1) symptom management, (2) caregiver needs, (3) early palliative care, and (4) care in the end-of-life phase. An international panel of palliative care experts in neuro-oncology synthesized the literature and reported the most relevant updates. A total of 140 articles were included. Results New insights include that: Hippocampal avoidance and stereotactic radiosurgery results in a lower risk of neurocognitive decline in patients with brain metastases; levetiracetam is more efficacious in reducing seizures than valproic acid as first-line monotherapy antiseizure drug (ASD) in glioma patients; lacosamide and perampanel seem well-tolerated and efficacious add-on ASDs; and a comprehensive framework of palliative and supportive care for high-grade glioma patients and their caregivers was proposed. No pharmacological agents have been shown in randomized controlled trials to significantly improve fatigue or neurocognition. Conclusions Since the 2017 EANO palliative care guidelines, new insights have been reported regarding symptom management and end-of-life care, however, most recommendations remain unchanged. Early palliative care interventions are essential to define goals of care and minimize symptom burden in a timely fashion. Interventional studies that address pain, fatigue, and psychiatric symptoms as well as (the timing of) early palliative care are urgently needed.